Human prostate adenocarcinoma (CaP) and benign prostatic hyperplasia (BPH) have epithelial and stromal cell origins, respectively. To determine whether the androgen signal is processed differently in these cell types the expression of transcripts for enzymes that control ligand access to the androgen receptor (AR) were measured. Transcripts for type 2 5α-reductase, ketosteroid reductases [aldo-keto reductase (AKR)1C1-AKR1C4], the major oxidative 3α-hydroxysteroid dehydrogenase (HSD) retinol dehydrogenase (RODH)-like 3α-HSD (RL-HSD) and nuclear receptors [AR, estrogen receptor (ER)α, and ERβ] were determined in whole human prostate and in cultures of primary epithelial cells (PEC) and primary stromal cells (PSC) from normal prostate, CaP and BPH by real-time RT-PCR. Normal PEC (n = 14) had higher levels of AKR1C1 (10-fold, P < 0.001), AKR1C2 (115-fold, P < 0.001) and AKR1C3 (6-fold, P < 0.001) than normal PSC (n = 15), suggesting that reductive androgen metabolism occurs. By contrast, normal PSC had higher levels of AR (8-fold, P < 0.001) and RL-HSD (21-fold, P < 0.001) than normal PEC, suggesting that 3α-androstanediol is converted to 5α-dihydrotestosterone to activate AR. In CaP PEC (n = 14), no significant changes in transcript levels vs. normal PEC were observed. In BPH PSC (n = 21) transcripts for AR (2-fold, P < 0.001), AKR1C1 (4-fold, P < 0.001), AKR1C2 (10-fold P < 0.001), AKR1C3 (4-fold, P < 0.001) and RL-HSD (3-fold, P < 0.003) were elevated to increase androgen response. Differences in the AR:ERβ transcript ratios (eight in normal PEC vs. 280 in normal PSC) were maintained in PEC and PSC in diseased prostate. These data suggest that CaP may be more responsive to an ERβ agonist and BPH may be more responsive to androgen ablation.
Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells